Adenomatous Polyposis Coli (APC) proteins are tumor suppressors known for their roles in Wnt signaling and cytoskeletal regulation. APC proteins function in many developmental processes and mutations in APC are present in ~80% of colon cancers. Recent research identified important cytoskeletal functions of APC including regulating mitotic spindle orientation, spindle attachment, and prevention of chromosomal instability. Because defects in these cytoskeletal processes are potentially oncogenic, the dual roles of APC in Wnt and cytoskeleton regulation may underlie APC's significance as a tumor suppressor. The mechanisms by which APC regulates the cytoskeleton remain unclear. We hypothesize they are based on APC localization and its interaction with microtubules, the actin cytoskeleton, and other cytoskeletal regulators. To further our understanding of APC in cytoskeletal regulation I will use Drosophila APC to address a series of key questions. Which regions of the APC protein participate in its cytoskeletal functions? Is APC function in Wnt signaling related to its cytoskeletal roles? Is localization of APC important for its cytoskeletal functions? What are the relevant partners of APC in regulating the cytoskeleton? Answering these questions will provide a more complete understanding of APC's role in both normal development and cancer. PUBLIC HEALTH RELEVANCE: Mutations in Adenomatous Polyposis Coli (APC) are responsible for approximately 80% of colon cancers, and APC mutations have also been associated with several other forms of cancer. Elucidating the mechanisms by which APC proteins regulate important cellular processes and identifying APCs relevant protein partners should greatly improve our understanding of APCs role in cancer biology.